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Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation

Gold nanoparticles (AuNPs) are a focus of growing medical research applications due to their unique chemical, electrical and optical properties. Because of uncertain toxicity, “green” synthesis methods are emerging, using plant extracts to improve biological and environmental compatibility. Here we...

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Autores principales: Aborig, Mohamed, Malik, Paul R. V., Nambiar, Shruti, Chelle, Pierre, Darko, Johnson, Mutsaers, Anthony, Edginton, Andrea N., Fleck, Andre, Osei, Ernest, Wettig, Shawn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523871/
https://www.ncbi.nlm.nih.gov/pubmed/31013763
http://dx.doi.org/10.3390/pharmaceutics11040179
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author Aborig, Mohamed
Malik, Paul R. V.
Nambiar, Shruti
Chelle, Pierre
Darko, Johnson
Mutsaers, Anthony
Edginton, Andrea N.
Fleck, Andre
Osei, Ernest
Wettig, Shawn
author_facet Aborig, Mohamed
Malik, Paul R. V.
Nambiar, Shruti
Chelle, Pierre
Darko, Johnson
Mutsaers, Anthony
Edginton, Andrea N.
Fleck, Andre
Osei, Ernest
Wettig, Shawn
author_sort Aborig, Mohamed
collection PubMed
description Gold nanoparticles (AuNPs) are a focus of growing medical research applications due to their unique chemical, electrical and optical properties. Because of uncertain toxicity, “green” synthesis methods are emerging, using plant extracts to improve biological and environmental compatibility. Here we explore the biodistribution of green AuNPs in mice and prepare a physiologically-based pharmacokinetic (PBPK) model to guide interspecies extrapolation. Monodisperse AuNPs were synthesized and capped with epigallocatechin gallate (EGCG) and curcumin. 64 CD-1 mice received the AuNPs by intraperitoneal injection. To assess biodistribution, groups of six mice were sacrificed at 1, 7, 14, 28 and 56 days, and their organs were analyzed for gold content using inductively coupled plasma mass spectrometry (ICP-MS). A physiologically-based pharmacokinetic (PBPK) model was developed to describe the biodistribution data in mice. To assess the potential for interspecies extrapolation, organism-specific parameters in the model were adapted to represent rats, and the rat PBPK model was subsequently evaluated with PK data for citrate-capped AuNPs from literature. The liver and spleen displayed strong uptake, and the PBPK model suggested that extravasation and phagocytosis were key drivers. Organ predictions following interspecies extrapolation were successful for rats receiving citrate-capped AuNPs. This work lays the foundation for the pre-clinical extrapolation of the pharmacokinetics of AuNPs from mice to larger species.
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spelling pubmed-65238712019-06-04 Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation Aborig, Mohamed Malik, Paul R. V. Nambiar, Shruti Chelle, Pierre Darko, Johnson Mutsaers, Anthony Edginton, Andrea N. Fleck, Andre Osei, Ernest Wettig, Shawn Pharmaceutics Article Gold nanoparticles (AuNPs) are a focus of growing medical research applications due to their unique chemical, electrical and optical properties. Because of uncertain toxicity, “green” synthesis methods are emerging, using plant extracts to improve biological and environmental compatibility. Here we explore the biodistribution of green AuNPs in mice and prepare a physiologically-based pharmacokinetic (PBPK) model to guide interspecies extrapolation. Monodisperse AuNPs were synthesized and capped with epigallocatechin gallate (EGCG) and curcumin. 64 CD-1 mice received the AuNPs by intraperitoneal injection. To assess biodistribution, groups of six mice were sacrificed at 1, 7, 14, 28 and 56 days, and their organs were analyzed for gold content using inductively coupled plasma mass spectrometry (ICP-MS). A physiologically-based pharmacokinetic (PBPK) model was developed to describe the biodistribution data in mice. To assess the potential for interspecies extrapolation, organism-specific parameters in the model were adapted to represent rats, and the rat PBPK model was subsequently evaluated with PK data for citrate-capped AuNPs from literature. The liver and spleen displayed strong uptake, and the PBPK model suggested that extravasation and phagocytosis were key drivers. Organ predictions following interspecies extrapolation were successful for rats receiving citrate-capped AuNPs. This work lays the foundation for the pre-clinical extrapolation of the pharmacokinetics of AuNPs from mice to larger species. MDPI 2019-04-12 /pmc/articles/PMC6523871/ /pubmed/31013763 http://dx.doi.org/10.3390/pharmaceutics11040179 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aborig, Mohamed
Malik, Paul R. V.
Nambiar, Shruti
Chelle, Pierre
Darko, Johnson
Mutsaers, Anthony
Edginton, Andrea N.
Fleck, Andre
Osei, Ernest
Wettig, Shawn
Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation
title Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation
title_full Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation
title_fullStr Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation
title_full_unstemmed Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation
title_short Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation
title_sort biodistribution and physiologically-based pharmacokinetic modeling of gold nanoparticles in mice with interspecies extrapolation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523871/
https://www.ncbi.nlm.nih.gov/pubmed/31013763
http://dx.doi.org/10.3390/pharmaceutics11040179
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